The fragile X (fra X) syndrome is one of the most important genetic conditions associated with neuropsychiatric disability in children. Recent findings have clarified the molecular mechanisms underlying the fra X syndrome and new DNA-based tests now make it feasible to test for the fra X mutation in large, clinically-relevant populations of children with behavior, learning and developmental problems. The overall goals of the research are to understand the extent to which the fra X mutation is a cause of behavior, learning and developmental dysfunction in children, to delineate the pattern of neuropsychiatric dysfunction caused by this condition and to define specific genetic factors associated with its severity. The following hypotheses will be tested: (1) the fra X mutation will be a frequent cause of neuropsychiatric disability in large clinic-derived samples consisting of school-age children with behavior and learning problems and preschool-age children referred for developmental delay, (2) when compared to DNA-negative controls from these same clinical samples, children with fra X will demonstrate greater dysfunction on measures assessing social disability, attention deficit hyperactivity disorder, stereotypic behavior, childhood affective/anxiety disorders, pervasive developmental disorder and visual-spatial deficits, (3) children with the fra X full mutation will have greater severity of behavioral and cognitive dysfunction compared to gender-matched children with the fra X premutation and fra X negative sibling controls and, (4) the size of the fra X full mutation in both males and females and X chromosome inactivation pattern in females will be significantly correlated with measures of behavioral and cognitive dysfunction. To test the first hypothesis, two large samples of children will be recruited and tested for the fra X mutation: (1) approximately 1,300 non-retarded, school-age children referred to a clinic for behavior and learning problems and, (2) approximately 600 preschool-age children referred to a clinic for language delay. Results from the DNA test will determine the proportion of children having fra X in the School-age and Preschool samples. To test the second hypothesis, children with the fra X mutation will be compared to DNA-negative control groups on specific measures assessing behavior, cognitive-developmental function and the presence of DSM-III-R diagnoses. To test hypothesis three, groups of children with the fra X full mutation, premutation and siblings who are DNA-negative will be recruited from families known to have one or more relatives with the fra X syndrome. These groups will be compared on specific measures assessing behavior, cognitive-developmental function and DSM-III-R diagnoses. To test hypothesis four, the size of the fra X mutation and X chromosome inactivation pattern will be determined using molecular genetic and imaging techniques. The association between these genetic variables and results obtained from the behavioral and cognitive assessment will be analyzed.